Stroke Rounds: Study Questions 'Obesity Paradox'

Action Points

Note that this Danish study suggests that overweight and obese patients are not protected from stroke-associated mortality compared with their normal-weight counterparts.

Be aware that some body mass index data had to be imputed, which could potentially bias these results.

Overweight and obese patients were not less likely -- or more likely -- to die from stroke compared with their normal-weight counterparts, a Danish study showed.

After accounting for missing data, the hazard ratio for death within 1 month of the stroke was 0.96 (95% CI 0.88-1.04) for those who were overweight and 1.0 (95% CI 0.88-1.13) for those who were obese, according to Tom Olsen, MD, PhD, of Frederiksberg University Hospital in Denmark, and colleagues.

The risk of stroke was, however, related to age, in that overweight patients had strokes 3 years earlier and obese patients 6 years earlier on average compared with those who had a normal weight, the researchers reported online in JAMA Neurology.

"Therefore, our study supports the recommendation to strive for normal weight because overweight status and obesity, while associated with premature stroke, do not carry a significant survival advantage," they wrote.

Previous studies have observed lower mortality rates among patients with higher body mass indexes (BMIs) for multiple chronic conditions, including stroke, but the reason for such an "obesity paradox" remains unclear.

"It might be the result of a balance between the disadvantages associated with obesity that lead to stroke and the benefits associated with obesity that promote survival after clinical illness," Olsen and colleagues wrote.

But, they added, "The paradox has also been explained as an artificial finding that is simply due to selection bias. If stroke or any other disease in obese patients with stroke is less severe than in patients of normal weight, obese patients with stroke would have a lower risk for dying of any disease, leaving the false impression that obesity constitutes a survival advantage."

They attempted to account for such selection bias in the current study by examining only deaths related to the index stroke -- defined as those occurring within the first month with a "death by stroke" designation on the death certificate. Their analysis used information from the Danish Stroke Register, which tracks stroke hospitalizations across the country, and the Danish Registry of Causes of Death.

The study included 71,617 patients hospitalized for stroke after excluding those with subarachnoid hemorrhage or transient ischemic attack and those younger than 20. The researchers used multiple imputation to account for the patients who did not have BMI information available.

Overall, 11% of the patients died within the first month, and most of those deaths (70%) were determined to be from the stroke.

BMI was inversely related both to the average age at stroke onset and to the severity of stroke (P<0.001). But elevated BMI was not associated with the risk of dying within 1 month of the stroke after adjustments were made for age, sex, stroke severity, stroke subtype, civil status, cardiovascular risk factors, duration of education, and income and missing BMI data was imputed.

Being underweight, however, was associated with a higher risk of stroke death (HR 1.16, 95% CI 1.06-1.26).

The findings were similar when the analysis was confined to deaths that occurred in the first week after a stroke.

The authors acknowledged some limitations of the study, including the incomplete coverage of the national registry of stroke admissions, missing BMI data for roughly 18,000 patients, and the possibility of bias related to variables that were not included in the registry.